It has been established over the last years that a number of diseases inter alia affect the intestinal microbiota. An example in this respect is colorectal cancer (Zhu et al., “Gut microbiota and probiotics in colon tumorigeneses”, Cancer Letters, 2011, Vol. 309, pages 119-127). Further, it is known that a number of diseases increase the susceptibility for bacterial translocation resulting inter alia in peritonitis, (such as e.g. cirrhosis) or in systemic inflammatory response syndrome (SIRS) or sepsis (such as e.g. pancreatitis, cholangitis, burn injury or trauma) (Gatt et a., “Review article: bacterial translocation in the critically ill—evidence and methods of prevention”, Aliment Pharmacol Ther 25, pages 741-757).
It has further been established that the intestinal microbiota plays an important role in several essential processes in the human body; thus, the microbiota inter alia performs a protective function, a metabolic function and a structural function. An impaired intestinal microbiota may thus result in changes in the metabolic profile, impairment of GI transit and pathogen overgrowth. Treatment regimens for diseases affecting the intestinal microbiota may include the administration of probiotics in order to restore or at least improve the impaired intestinal microbiota.
Patients suffering from a disease resulting in an impaired microbiota or increasing the susceptibility for intestinal bacterial translocation may not only suffer from the underlying disease but also from pain due to various reasons. Thus, a patient suffering from colorectal cancer may also suffer from severe back pain, wherein said back pain may have a completely different origin. The back pain may be that severe that the patient requires a long term analgesic therapy.
Opioids correspond to the most efficient analgesics if moderate to severe pain requires treatment. However, several side effect of opioid therapy are known; one of the most prominent side effects is opioid-induced constipation, which is also affecting the GI-tract.
If one were to treat the above mentioned patient suffering from colorectal cancer and back pain with an opioid, it can be expected that the impaired microbiota will likely not improve but, to the contrary, rather worsen. The same is true for a patient suffering from pain and a disease, which increases the risk for intestinal bacterial translocation; the use of an opioid in such a patient will even further increase the susceptibility to intestinal bacterial translocation. Further, patients suffering from pancreatitis, cholangitis, burn injury or trauma may be more susceptible to bacterial translocation resulting in systemic inflammatory response syndrome (SIRS) or sepsis; the use of an opioid in such patients will even further increase the susceptibility to systemic inflammatory response syndrome (SIRS) or sepsis. As a consequence, opioids may not be used for pain treatment in such patients, resulting in the undertreatment of pain.
It is evident from the above that there is a need for a pharmaceutical composition, which is capable of treating pain in a patient suffering from pain and a further disease, which is negatively affecting the intestinal microbiota and/or increasing the susceptibility for intestinal bacterial translocation (resulting inter alia in peritonitis), wherein the pharmaceutical composition fails to have a negative impact on the intestinal microbiota and may even improve the intestinal microbiota and/or decrease the risk for intestinal bacterial translocation.